Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Overexpression of HOXB4 confers a myelo-erythroid differentiation delay in vitro

Leukemia volume 19, pages 148–153 (2005)Cite this article

TO THE EDITOR

Ectopic delivery of HOXB4 increases the proliferative potential of both murine and human bone marrow cells (BMC), and results in an enhanced rate of haemopoietic reconstitution to apparently normal steady-state levels.1 Moreover, retroviral delivery of HOXB4 facilitates the in vitro expansion of BMC with repopulating activity, as does the provision of recombinant HOXB4 protein.2, 3 These data establish a role for HOXB4 in the self-renewal of haemopoietic stem cells (HSC), and highlight the potential of HOXB4 to improve cellular therapies using HSC. To date, the biological processes affected by HOXB4 are not fully defined. It is of great importance to understand these, and the potential sequelae to HOXB4 overexpression, if this is to prove useful clinically. Here we demonstrate for the first time that ectopic HOXB4 expression inhibits the differentiation of primary murine BMC and a myeloid progenitor cell line. Using detailed kinetic analysis, we additionally define that this disruption results not from a complete block of differentiation, but from a reduction in the rate of commitment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Sauvageau G, Thorsteinsdottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM et al Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 1995; 9: 1753–1765.

    Article  CAS  Google Scholar 

  2. Antonchuk J, Sauvageau G, Humphries RK . HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 2002; 109: 39–45.

    Article  CAS  Google Scholar 

  3. Krosl J, Austin P, Beslu N, Kroon E, Humphries RK, Sauvageau G . In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nat Med 2003; 9: 1428–1432.

    Article  CAS  Google Scholar 

  4. Milsom MD, Woolford LB, Margison GP, Humphries RK, Fairbairn LJ . Enhanced in vivo selection of bone marrow cells by retroviral-mediated co-expression of mutant O6-Methylguanine-DNA-Methyltransferase and HOXB4. Mol Ther 2004; 10: 861–872.

    Article  Google Scholar 

  5. Spooncer E, Heyworth CM, Dunn A, Dexter TM . Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation 1986; 31: 111–118.

    Article  CAS  Google Scholar 

  6. Mazurier F, Doedens M, Gan OI, Dick JE . Characterization of cord blood hematopoietic stem cells. Ann N Y Acad Sci 2003; 996: 67–71.

    Article  Google Scholar 

  7. Pierce A, Spooncer E, Ainsworth S, Whetton AD . BCR-ABL alters the proliferation and differentiation response of multipotent hematopoietic cells to stem cell factor. Oncogene 2002; 21: 3068–3075.

    Article  CAS  Google Scholar 

  8. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P et al LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302: 415–419.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Jeff Barry and Mike Hughes for FACS analysis, Lorna Woolford for technical assistance and Stella Pearson for advice. This work was funded by Cancer Research UK (LJF, MDM, DG). RD was a recipient of a Wellcome Trust Vacation Scholarship. MDM received an ICRETT award from the International Union Against Cancer (UICC) to fund a sabbatical in the laboratory of CvK.

Author information

Authors and Affiliations

  1. Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK

    M D Milsom, R Duxbury, D Gagen & L J Fairbairn

  2. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada

    R K Humphries

  3. Department of Internal Medicine, University of Freiburg, Freiburg, Germany

    M Schmidt & C von-Kalle

  4. Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    C von-Kalle

Authors
  1. M D Milsom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Duxbury
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Gagen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R K Humphries
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C von-Kalle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L J Fairbairn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L J Fairbairn.

Additional information

Supplementary Information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Milsom, M., Duxbury, R., Gagen, D. et al. Overexpression of HOXB4 confers a myelo-erythroid differentiation delay in vitro. Leukemia 19, 148–153 (2005). https://doi.org/10.1038/sj.leu.2403554

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403554

Search

Advanced search

Quick links